Human organic anion transporting polypeptide 1B3 (OATP1B3) is more heavily N-glycosylated than OATP1B1 in extracellular loops 2 and 5.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Liang T;Liang T; Liu H; Liu H; Li L; Li L; Huan R; Huan R; Gui C; Gui C
  • Source:
    International journal of biological macromolecules [Int J Biol Macromol] 2024 Oct; Vol. 278 (Pt 2), pp. 134748. Date of Electronic Publication: 2024 Aug 13.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: Guildford, Eng., IPC Science and Technology Press.
    • Subject Terms:
      Liver-Specific Organic Anion Transporter 1*/metabolism ; Solute Carrier Organic Anion Transporter Family Member 1B3*/metabolism ; Solute Carrier Organic Anion Transporter Family Member 1B3*/genetics; Glycosylation ; Humans ; HEK293 Cells
    • Abstract:
      Human organic anion transporting polypeptide 1B3 (OATP1B3) and 1B1 are two liver-specific and highly homologous uptake transporters, whose structures consist of 12 transmembrane domains. The present study showed that OATP1B3 is more heavily N-glycosylated than OATP1B1 in extracellular loop 2 (EL2) and EL5. OATP1B3 has six N-glycosylation sites, namely N134, N145, N151, N445, N503, and N516, which is twice of that of OATP1B1. Single removal of individual N-glycans seems to have minimal influence on the surface expression and function of OATP1B3. However, simultaneous removal of all N-glycans will lead to OATP1B3's large retention in the endoplasmic reticulum and cellular degradation and thus significantly disrupts its surface expression. While N-glycosylation plays a crucial role in the surface expression of OATP1B3, it also has some effect on the transport function of OATP1B3 per se, which is not due to a decrease of substrate binding affinity but due to a reduced transporter's turnover number. Taken together, N-glycosylation is essential for normal surface expression and function of OATP1B3. Its disruption by some liver diseases such as NASH might alter the pharmacokinetic/pharmacodynamic properties of OATP1B3's substrate drugs.
      Competing Interests: Declaration of competing interest The authors have no competing interest to declare.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Extracellular loop; Function; N-glycosylation; OATP; Surface expression
    • Accession Number:
      0 (Liver-Specific Organic Anion Transporter 1)
      0 (Solute Carrier Organic Anion Transporter Family Member 1B3)
      0 (SLCO1B3 protein, human)
      0 (SLCO1B1 protein, human)
    • Publication Date:
      Date Created: 20240815 Date Completed: 20240917 Latest Revision: 20241108
    • Publication Date:
      20241108
    • Accession Number:
      10.1016/j.ijbiomac.2024.134748
    • Accession Number:
      39147348